A regular feature of cells in most tumours is an abnormal number of chromosomes – a feature known as aneuploidy. A key mechanism towards this state is whole chromosome mis-segregation (CMS), whose role in cancer is still debated. For a long time, CMS was considered a side effect of oncogenesis, however recent research suggests instead a role as a key initiating driver of malignant transformation. Specifically, whether the mechanism of CMS can lead to the kind of mutational signature observed in early stage tumours is unknown. Furthermore, the signalling pathways themselves are still being elucidated, and the impact that these different mechanisms have on the network are yet not defined. Because of the high biological complexity, experimental limitations and overall uncertainty, ALife methods are well suited to untangle the role of CMS and shed light on its role in oncogenesis. Here we investigate the effects that CMS and point mutation have on a biologically inspired genome, implemented in silico though a gene-regulatory network (GRN) within an agent-based model (ABM). Importantly, the implementation aims to mimic real biology to facilitate possible emergent features. Each cell is equipped with chromosomes containing abstractions of key interconnected genes that are known to play a role in many cancers. We compare the effects of random mutations, where a gene is functionally altered, against CMS, where many genes are lost or gained simultaneously. Our results show that CMS is a viable mechanism for oncogenesis. Comparing CMS with the more traditional view of mutation accumulation, we show that both share similar emergent phenotypes, but that they are genotypically different. We highlight that loss of tumour suppression by either means might be the first step towards oncogenesis, and conclude that cancers probably utilize these two mechanisms in tandem. Finally, we propose that measurements of these aberrations could help to better characterize the evolution of tumours.